RESUMEN
A drug-drug interaction (DDI) trial of cytochrome P450 3A (CYP3A) is a necessary part of early-phase trials of drugs mainly metabolized by this enzyme, but CYP3A DDI clinical trials do not have a standard design, especially for Chinese people. We aimed to offer specific recommendations for CYP3A DDI clinical trial design. This was an open, three-cycle, self-controlled study. Healthy subjects were given different administration strategies of CYP3A4 perpetrators. In each cycle, blood samples were collected before and within 24 h after the administration of midazolam, the CYP3A indicator substrate. The plasma concentrations of midazolam and 1-hydroxymidazolam was obtained using liquid chromatography tandem mass spectrometry assay. For CYP3A inhibition, itraconazole exposure with a loading dose could increase the exposure of midazolam by 3.21-fold based on maximum plasma concentration (Cmax), 8.37-fold based on area under the curve Pharmacology Research & Perspectives for review only from zero to the time point (AUC0-t), and 11.22-fold based on area under the curve from zero to infinity (AUC0-∞). The data were similar for itraconazole pretreatment without a loading dose. For CYP3A induction, the exposure of rifampin for 7 days decreased the plasma concentration of midazolam ~0.27-fold based on Cmax, ~0.18-fold based on AUC0-t, and ~0.18-fold based on AUC0-∞. Midazolam exposure did not significantly change when the pretreatment of rifampin increased to 14 days. This study showed that itraconazole pretreatment for 3 days without a loading dose was enough for CYP3A inhibition, and pretreatment with rifampin for 7 days could induce near-maximal CYP3A levels.
Asunto(s)
Pueblo Asiatico , Inhibidores del Citocromo P-450 CYP3A , Citocromo P-450 CYP3A , Interacciones Farmacológicas , Itraconazol , Midazolam , Humanos , Midazolam/farmacocinética , Midazolam/administración & dosificación , Midazolam/sangre , Midazolam/análogos & derivados , Itraconazol/farmacología , Itraconazol/administración & dosificación , Citocromo P-450 CYP3A/metabolismo , Masculino , Adulto , Inhibidores del Citocromo P-450 CYP3A/farmacología , Inhibidores del Citocromo P-450 CYP3A/administración & dosificación , Adulto Joven , Rifampin/farmacología , Rifampin/administración & dosificación , Voluntarios Sanos , Femenino , Inductores del Citocromo P-450 CYP3A/farmacología , Área Bajo la Curva , Proyectos de Investigación , Ensayos Clínicos como Asunto , Pueblos del Este de AsiaRESUMEN
The aim of our study is to explore the mechanism of transcription-4 (STAT4) in acute myeloid leukemia (AML). STAT4 level in AML bone marrow samples/cells was analyzed using bioinformatics and quantitative real-time PCR. The correlation between high STAT4 expression and the prognosis of AML patients was analyzed. The viability, apoptosis, and angiogenesis of AML cells were detected. The levels of STAT4, vascular endothelial growth factor A (VEGFA), and apoptosis-related proteins (Bcl-2 and Bax) in transfected AML cells were examined. STAT4 level was upregulated in AML. STAT4 silencing decreased the viability and angiogenesis, yet increased the apoptosis of AML cells, while overexpressed STAT4 did conversely. VEGFA silencing counteracted the impacts of overexpressed STAT4 upon promoting viability and angiogenesis as well as repressing the apoptosis of AML cells. High STAT4 expression was correlated with poor prognosis of AML patients and facilitated disease progression via upregulating VEGFA expression.
RESUMEN
Dunaliella salina, a microalga that thrives under high-saline conditions, is notable for its high ß-carotene content and the absence of a polysaccharide cell wall. These unique characteristics render it a prime candidate as a cellular platform for astaxanthin production. In this study, our initial tests in an E. coli revealed that ß-ring-4-dehydrogenase (CBFD) and 4-hydroxy-ß-ring-4-dehydrogenase (HBFD) genes from Adonis aestivalis outperformed ß-carotene hydroxylase (BCH) and ß-carotene ketolase (BKT) from Haematococcus pluvialis counterparts by two-fold in terms of astaxanthin biosynthesis efficiency. Subsequently, we utilized electroporation to integrate either the BKT gene or the CBFD and HBFD genes into the genome of D. salina. In comparison to wild-type D. salina, strains transformed with BKT or CBFD and HBFD exhibited inhibited growth, underwent color changes to shades of red and yellow, and saw a nearly 50% decline in cell density. HPLC analysis confirmed astaxanthin synthesis in engineered D. salina strains, with CBFD + HBFD-D. salina yielding 134.88 ± 9.12 µg/g of dry cell weight (DCW), significantly higher than BKT-D. salina (83.58 ± 2.40 µg/g). This represents the largest amount of astaxanthin extracted from transgenic D. salina, as reported to date. These findings have significant implications, opening up new avenues for the development of specialized D. salina-based microcell factories for efficient astaxanthin production.
Asunto(s)
Xantófilas , Xantófilas/metabolismo , Chlorophyceae/metabolismo , Chlorophyceae/genética , Vías Biosintéticas/genética , Chlorophyta/metabolismo , Chlorophyta/genética , Escherichia coli/metabolismo , Escherichia coli/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Oxigenasas de Función Mixta , OxigenasasRESUMEN
Breast cancer is one of the most common malignant tumors affecting women worldwide. Breast cancer is a complex disease characterized by abnormal growth of cells in the breast tissue. Metastasis, the spread of cancer cells from the primary tumor site to distant organs, is a major challenge in the management of breast cancer. Although metastasis to distant sites is a well-known feature of breast cancer, scalp involvement is relatively rare. The occurrence of scalp metastasis signifies an advanced stage of the disease. The 51-year-old female discovered a firm, painless mass in her right breast that had been there for two years. It had been pricking for a month, and the biopsy revealed that the mass was invasive carcinoma of the right breast. Imaging tests suggested that the tumor was malignant. Adjuvant endocrine therapy and postoperative adjuvant chemotherapy were administered following a modified radical resection for breast cancer. Eleven months later, radiation treatment and replace endocrine therapy was used. 32 months following surgery, a scalp tumor was discovered; a pathology biopsy verified the origin of the breast cancer; three months later, bone, brain, and visceral metastases were discovered. After that, she received oral capecitabine treatment and was admitted into the hospital for advanced rescue treatment. She is currently in the disease stability state, her disease is effectively managed, and no new metastatic lesions have been discovered.
RESUMEN
PURPOSE: Breast cancer (BC) is a devastating disease for women. Microbial influences may be involved in the development and progression of breast cancer. This study aimed to investigate the difference in intestinal flora abundance between breast cancer patients and healthy controls (HC) based on previous 16S ribosomal RNA (rRNA) gene sequencing results, which have been scattered and inconsistent in previous studies. MATERIALS AND METHODS: In agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we searched for pertinent literature in Pubmed, Embase, Cochrane Library, and Web of Science databases from build until February 1, 2023. Relative abundance, diversity of intestinal microflora by level, microbial composition, community structure, diversity index, and other related data were extracted. We used a fixed or random effects model for data analysis. We also conducted funnel plot analysis, sensitivity analysis, Egger's, and Begg's tests to assess the bias risk. RESULTS: A total of ten studies involving 734 BC patients were enrolled. It was pointed out that there were significant differences in the Chao index between BC and HC in these studies [SMD = - 175.44 (95% CI - 246.50 to - 104.39)]. The relative abundance of Prevotellaceae [SMD = - 0.27 (95% CI - 0.39 to - 0.15)] and Bacteroides [SMD = 0.36 (95% CI 0.23-0.49)] was significantly different. In the included articles, the relative abundance of Prevotellaceae, Ruminococcus, Roseburia inulinivorans, and Faecalibacterium prausnitzii decreased in BC. Accordingly, the relative richness of Erysipelotrichaceae was high in BC. CONCLUSIONS: This observational meta-analysis revealed that the changes in gut microbiota were correlated with BC, and the changes in some primary fecal microbiota might affect the beginning of breast cancer.
Asunto(s)
Neoplasias de la Mama , Heces , Microbioma Gastrointestinal , ARN Ribosómico 16S , Humanos , Neoplasias de la Mama/microbiología , ARN Ribosómico 16S/genética , Femenino , Microbioma Gastrointestinal/genética , Heces/microbiologíaRESUMEN
BACKGROUND: The novel coronavirus pneumonia (COVID-19) is an infectious disease caused by the infection of a novel coronavirus known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has resulted in millions of deaths. We aimed to evaluate the safety and immunogenicity of the COVID-19 mRNA vaccine (CS-2034, CanSino, Shanghai, China) in adults without COVID-19 infection from China. METHOD: This is a multicenter Phase I clinical trial with a randomized, double-blinded, dose-exploration, placebo-controlled design. The trial recruited 40 seronegative participants aged 18-59 years who had neither received any COVID-19 vaccine nor been infected before. They were divided into a low-dose group (administered with either the CS-2034 vaccine containing 30 µg of mRNA or a placebo of 0.3 ml type 5 adenovirus vector) and a high-dose group (administered with either the CS-2034 vaccine containing 50 µg of mRNA or a placebo of 0.5 ml type 5 adenovirus vector). Participants were randomly assigned in a 3:1 ratio to receive either the mRNA vaccine or a placebo on days 0 and 21 according to a two-dose immunization schedule. The first six participants in each dosage group were assigned as sentinel subjects. Participants were sequentially enrolled in a dose-escalation manner from low to high dose and from sentinel to non-sentinel subjects. Blood samples were collected from all participants on the day before the first dose (Day 0), the day before the second dose (day 21), 14 days after the second dose (day 35), and 28 days after the second dose (day 49) to evaluate the immunogenicity of the CS-2034 vaccine. Participants were monitored for safety throughout the 28-day follow-up period, including solicited adverse events, unsolicited adverse events, adverse events of special interest (AESI), and medically attended adverse events (MAE). This report focuses solely on the safety and immunogenicity analysis of adult participants aged 18-59 years, while the long-term phase of the study is still ongoing. This study is registered at ClinicalTrials.gov, NCT05373485. FINDINGS: During the period from May 17, 2022, to August 8, 2022, a total of 155 participants aged 18-59 years were screened for this study. Among them, 115 participants failed the screening process, and 40 participants were randomly enrolled (15 in the low-dose group, 15 in the high-dose group, and 10 in the placebo group). Throughout the 28-day follow-up period, the overall incidence of adverse reactions (related to vaccine administration) in the low-dose group, high-dose group, and placebo group was 93.33% (14/15), 100.00% (15/15), and 80.00% (8/10), respectively. There was a statistically significant difference in the incidence of local adverse reactions (soreness, pruritus, swelling at the injection site) among the low-dose group, high-dose group, and placebo group (P = 0.002). All adverse reactions were mainly of severity grade 1 (mild) or 2 (moderate), and no adverse events of severity grade 4 or higher occurred. Based on the analysis of Spike protein Receptor Binding Domain (S-RBD) IgG antibodies against the BA.1 strain, the seroconversion rates of antibodies at day 21 after the first dose were 86.67%, 93.33%, and 0.00% in the low-dose group, high-dose group, and placebo group, respectively. The geometric mean titer (GMT) of antibodies was 61.2(95%CI 35.3-106.2), 55.4(95%CI 36.3-84.4), and 15.0(95%CI 15.0-15.0), and the geometric mean fold increase (GMI) was 4.08(95%CI 2.35-7.08), 3.69(95%CI 2.42-5.63), and 1.00(95%CI 1.00-1.00) for each group. At day 28 after the full vaccination, the seroconversion rates of antibodies were 100.00%, 93.33%, and 0.00%, and the GMT of antibodies was 810.0(95%CI 511.4-1283.0), 832.2(95%CI 368.1-1881.6), and 15.0(95%CI 15.0-15.0), and the GMI was 54.00(95%CI 34.09-85.53), 55.48(95%CI 24.54-125.44), and 1.00(95%CI 1.00-1.00) for each group, respectively. Based on the analysis of CD3+/CD4+ cell cytokine response, the percentages of IL-2+, IL-4+, IFN-γ+, and TNF-α+ cells increased after 14 days and 28 days of full vaccination in both the low-dose group and high-dose group. The increase was most pronounced in the high-dose group. INTERPRETATION: At day 28 after the full vaccination, both the low-dose and the high-dose CS-2034 vaccine were able to induce the production of high titers of S-RBD IgG antibodies against the BA.1 strain. Adverse reactions in the low-dose and high-dose groups were mainly of severity grade 1 or 2, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Inmunogenicidad Vacunal , Adulto , Humanos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , China , COVID-19/prevención & control , Vacunas contra la COVID-19/uso terapéutico , Método Doble Ciego , Pueblos del Este de Asia , Inmunoglobulina G , ARN Mensajero , SARS-CoV-2 , Vacunas Sintéticas/uso terapéutico , Vacunas de ARNmRESUMEN
The dietary needs of calcium (Ca) and phosphorus (P) are interdependent, thus accurate evaluation of Ca and P requirements of broilers to support skeleton health and optimal growth is critical. The present study was carried out to investigate the effects of dietary Ca and nonphytate P (NPP) levels and their interactions on growth performance, tibiotarsus characteristics, tibiotarsus metabolism-related enzyme and proteins, and their gene expression of broilers, so as to provide a rational recommendation for Ca and NPP levels in diet. A total of 540 one-day-old Arbor Acres male broilers were randomly allotted to 1 of 15 treatments with 6 replicate cages of 6 birds per cage for each treatment in a completely randomized design involving a 5 × 3 factorial arrangement of treatments (5 levels of Ca × 3 levels of NPP). The birds were fed the corn-soybean meal diet containing 0.60%, 0.70%, 0.80%, 0.90%, or 1.00% Ca and 0.35%, 0.40%, or 0.45% NPP for 21 d. Dietary Ca level affected (P < 0.03) the bone mineral density, bone mineral content (BMC), breaking strength, ash percentage and ash Ca contents in tibia, which showed linear (P < 0.006) responses to dietary Ca levels. Dietary NPP level affected (P < 0.05) tibia BMC, ash percentage, and FGF23 mRNA level. Broilers that received 0.40% and 0.45% NPP had higher (P < 0.04) tibia BMC and ash percentage than those that received 0.35% NPP, but no differences (P > 0.05) were found between 0.40% and 0.45% NPP. Broilers that received 0.40% NPP had higher (P = 0.02) tibia FGF23 mRNA level than those that received 0.35% NPP, but no differences (P > 0.05) were detected between 0.40% and 0.45% NPP or 0.45% and 0.35% NPP. The interactions between dietary Ca and NPP affected (P < 0.05) ADG, ALP activity, bone gal protein, FGF23 contents, and the mRNA expression levels ALP and bone gal protein in tibia of broilers. Results from the present study indicate that dietary Ca and NPP interaction influences growth, tibiotarsus development, and related gene expression of broiler chickens. Considering all the criteria, the dietary levels of 0.90% Ca and 0.45% NPP would be optimal for both growth and tibiotarsus development of broilers fed a conventional corn-soybean meal diet from 1 to 21 d of age.
Asunto(s)
Calcio de la Dieta , Fósforo Dietético , Animales , Masculino , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Huesos/metabolismo , Calcio de la Dieta/metabolismo , Pollos , Dieta/veterinaria , Suplementos Dietéticos , Expresión Génica , Fósforo/metabolismo , Fósforo Dietético/metabolismoRESUMEN
PURPOSE: In this study, we aimed to explore the potential significance of AR expression in HER2-positive breast cancer patients who underwent neoadjuvant targeted therapy. Specifically, we investigated the correlation between AR expression levels and pathological complete response (pCR) rates. Our objective was to determine whether there were significant differences in pCR rates among HER2-positive breast cancer patients with different levels of AR expression. METHODS: We conducted a retrospective analysis of 258 HER-2 positive breast cancer patients who underwent neoadjuvant dual-blocked standard therapy (following the NCCN Guideline 2021) at three breast cancer centers in southwest China. We analyzed the clinicopathological features and pCR rates of these patients. The cut-off value for AR expression level was calculated as the median value of 70%. We used the chi-square test to investigate the correlation between AR expression level and pCR rate, as well as other clinicopathological features. RESULTS: Out of the 258 patients analyzed, 154 (59.69%) achieved pCR. Based on the cut-off value of 70%, AR expression level was classified as low (AR ≤ 70%) or high (AR > 70%) expression. Our analysis revealed a significant correlation between AR expression level and pCR rate in HER2-positive breast cancer patients (P = 0.031). We also found a significant association between pCR rate and clinical stage (P = 0.033) and chemotherapy regimen (P = 0.034). Furthermore, subgroup analyses showed that the pCR rate was higher in patients with high AR expression levels compared to those with low AR expression levels. Additionally, we observed that patients with an ER/AR ratio of less than 1 had a higher pCR rate than those with an ER/AR ratio greater than 1 (P = 0.038). CONCLUSION: Our study findings suggest that HER2-positive breast cancer patients with high AR expression levels may achieve higher pCR rates when treated with neoadjuvant dual-blocked therapy. Overall, our results support the idea that AR expression levels have a significant correlation with pCR rates in HER2-positive breast cancer patients receiving this particular form of treatment.
Asunto(s)
Neoplasias de la Mama , Receptores Androgénicos , Femenino , Humanos , Andrógenos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Terapia Neoadyuvante , Receptor ErbB-2/metabolismo , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Estudios RetrospectivosRESUMEN
In this work, the ß-cyclodextrin (ß-CD) was modified by a phosphazene compound to prepare a novel amorphous derivate (ß-CDCP), which was combined with the ammonium polyphosphate (APP) as a synergistic flame retardant (FR) of the bio-based poly(L-lactic acid) (PLA). The effects of the APP/ß-CDCP on the thermal stability, combustion behavior, pyrolysis process, fire resistance performance and crystallizability of the PLA were investigated comprehensively and in depth by thermogravimetric (TG) analysis, limited oxygen index (LOI) analysis, UL-94 test, cone calorimetry measurement, TG-infrared (TG-IR), scanning electron microscopy-energy dispersive spectrometer, Raman spectroscopy, pyrolysis-gas chromatography/mass spectrometry and differential scanning calorimetry. The PLA/5%APP/10%ß-CDCP showed a highest LOI of 33.2 %, passed V-0 rating and exhibited self-extinguish phenomenon in the UL-94 test. Also, it presented a lowest peak of heat release rate, total heat release, peak of smoke production rate and total smoke release, and a highest char yield treated by cone calorimetry analysis. In addition, the 5%APP/10%ß-CDCP shortened significantly crystallization time and enhanced crystallization rate of the PLA. Gas phase and intumescent condensed phase fire proofing mechanisms are proposed to elucidate enhanced fire resistance in this system in detail.
Asunto(s)
Oxígeno , Humo , Microesferas , Calorimetría , PoliésteresRESUMEN
Wearable bioelectronics are gaining extraordinary attention due to their capabilities to achieve continuous monitoring of human health status. However, mainstream manufacturing technologies, including photolithography and printing technology, limit current wearable bioelectronics on 2D planar structures with little surface area in contact with the body. It thus limits the amount of physiological information that current wearable bioelectronics could obtain. Furthermore, they need to be firmly attached to the body, affecting the wearing comfort. In this study, we leveraged the versatile thermal drawing process and developed a flexible microelectronic fiber with bioanalytical functions that could be woven into textiles as a new form of wearable bioelectronics. Within a single strand of fiber, we successfully integrated all-in-one multiplexed electrochemical sensing capabilities, with the sweat as the primary object. Adopting the laser micromachining technique, we developed biosensing functions on the longitudinal surface of the fiber with two sensing electrodes for Na+ and uric acid (UA), respectively, together with a pseudo reference electrode (p-RE). We carefully characterized the all-in-one multiplexed sensing performance of the fiber and demonstrated its successful application in sweat sensing based on its textile forms. The results show significant potential for application in wearable textiles for monitoring key health signals of humans.
Asunto(s)
Técnicas Biosensibles , Dispositivos Electrónicos Vestibles , Humanos , Sudor/química , Textiles , Electrodos , Técnicas Biosensibles/métodosRESUMEN
Microbial fuel cells (MFCs) can potentially be utilized for power generation, but their low power density and low energy storage capabilities remain major bottlenecks for their large-scale development. In this research, a simplistic nitrogen-doped hierarchically porous carbon material (HPC-A) was developed through a one-step carbonization and activation process and was successfully hot-pressed on the carbon cloth (CC) substrate. This process fabricates capacitive bioanodes (HPC-A-CC) that can enhance electricity generation and storage in MFCs. The as-prepared HPC-A-CC anode delivered a power density of 2043.6 mW·m-2 and a cumulative total charge (Qm) of 426.4 ± 13.4C·m-2 at each cycle, which was 2.1 and 34.8 times higher than that of the plain CC anode, respectively. This was a result of the hierarchical and interconnected porous structure, improved hydrophilic surface, and increased number of active centers which host the bacteria for enhanced electron transfer. Electrochemical measurements indicated the superior electrochemical activity and capacitive behavior of the HPC-A-CC anode. Furthermore, biofilm analysis revealed that the HPC-A-CC biofilm exhibited higher cell viability and a more uniform spatial distribution. These findings not only demonstrate the potential of HPC-A-CC for power enhancement in MFCs but also provide a feasible solution to the problem of power generation and demand mismatch in MFC applications.
Asunto(s)
Fuentes de Energía Bioeléctrica , Carbono/química , Nitrógeno , Porosidad , Electricidad , ElectrodosRESUMEN
Breast cancer is the most common female malignancy, but the mechanisms regulating gene expression leading to its development are complex. In recent years, as epigenetic research has intensified, RNA-binding proteins (RBPs) have been identified as a class of posttranscriptional regulators that can participate in regulating gene expression through the regulation of RNA stabilization and degradation, intracellular localization, alternative splicing and alternative polyadenylation, and translational control. RBPs play an important role in the development of normal mammary glands and breast cancer. Functional inactivation or abnormal expression of RBPs may be closely associated with breast cancer development. In this review, we focus on the function and regulatory mechanisms of RBPs in breast cancer, as well as the advantages and challenges of RBPs as potential diagnostic and therapeutic targets in breast cancer, and discuss the potential of RBPs in clinical treatment.
RESUMEN
Poly(L-lactic acid) (PLA) is a kind of important bio-macromolecule which can be prepared via fermentation of starch of maize and sweet potato. Flammability and extremely poor crystallizability limited its wide application. In this work, a novel Schiff base derivate (CP) was synthesized and, combined with ammonium polyphosphate (APP) as a synergistic flame retardant and nucleating agent to investigate its effects on LOI, UL-94 rating, thermal stability, combustion behavior and crystallizability of PLA. With loading of 5%CP/10%APP, PLA showed a significantly enhanced LOI and passed V-0 fire-safety rating with self-extinguish effect. PLA/5%CP/10%APP presented the lowest pHRR, THR and TSR, and highest char residue yield, FPI and FRI in cone calorimetry test, indicating an excellent flame retardancy effect, enhanced fire safety and longer escaping time in the fire. A continuous, compact and thick char layer structure formed as a protective barrier in combustion process, to enhance heat-insulating and oxygen resistance property, thermal stability and smoke-suppressing capacity of PLA. Flame retardancy mechanism was proposed and discussed based on comprehensive and in-depth characterization techniques. Also, 5%CP/10%APP presented a good nucleation effect to enormously increase crystallizability and shorten crystallization time of PLA.
Asunto(s)
Compuestos de Amonio , Retardadores de Llama , Bases de Schiff , Poliésteres/química , Polifosfatos/química , Compuestos de Amonio/químicaRESUMEN
Monocular 3D object detection is very challenging in autonomous driving due to the lack of depth information. This paper proposes a one-stage monocular 3D object detection network (MDS Net), which uses the anchor-free method to detect 3D objects in a per-pixel prediction. Firstly, a novel depth-based stratification structure is developed to improve the network's ability of depth prediction, which exploits the mathematical relationship between the size and the depth in the image of an object based on the pinhole model. Secondly, a new angle loss function is developed to further improve both the accuracy of the angle prediction and the convergence speed of training. An optimized Soft-NMS is finally applied in the post-processing stage to adjust the confidence score of the candidate boxes. Experiment results on the KITTI benchmark demonstrate that the proposed MDS-Net outperforms the existing monocular 3D detection methods in both tasks of 3D detection and BEV detection while fulfilling real-time requirements.
RESUMEN
Nowadays, bioelectronic devices are evolving from rigid to flexible materials and substrates, among which thermally-drawn-fiber-based bioelectronics represent promising technologies thanks to their inherent flexibility and seamless integration of multi-functionalities. However, electrochemical sensing within fibers remains a poorly explored area, as it imposes new demands for material properties-both the electrochemical sensitivity and the thermomechanical compatibility with the fiber drawing process. Here, we designed and fabricated microelectrode fibers made of carbon nanotube (CNT)-based hybrid nanocomposites and further evaluated their detailed electrochemical sensing performances. Carbon-black-impregnated polyethylene (CB-CPE) was chosen as the base material, into which CNT was loaded homogeneously in a concentration range of 3.8 to 10 wt%. First, electrical impedance characterization of CNT nanocomposites showed a remarkable decrease of the resistance with the increase in CNT loading ratio, suggesting that CNTs notably increased the effective electrical current pathways inside the composites. In addition, the proof-of-principle performance of fiber-based microelectrodes was characterized for the detection of ferrocenemethanol (FcMeOH) and dopamine (DA), exhibiting an ultra-high sensitivity. Additionally, we further examined the long-term stability of such composite-based electrode in exposure to the aqueous environment, mimicking the in vivo or in vitro settings. Later, we functionalized the surface of the microelectrode fiber with ion-sensitive membranes (ISM) for the selective sensing of Na+ ions. The miniature fiber-based electrochemical sensor developed here holds great potential for standalone point-of-care sensing applications. In the future, taking full advantage of the thermal drawing process, the electrical, optical, chemical, and electrochemical modalities can be all integrated together within a thin strand of fiber. This single fiber can be useful for fundamental multi-mechanistic studies for biological applications and the weaved fibers can be further applied for daily health monitoring as functional textiles.
Asunto(s)
Nanocompuestos , Nanotubos de Carbono , Fibra de Carbono , Dopamina , Microelectrodos , Nanotubos de Carbono/químicaRESUMEN
As the core of microbial fuel cells (MFCs), the components and structure of electroactive biofilms (EABs) are essential for MFC performance. Bacterial adhesion plays a vital role in shaping the structure of EABs, but the effect of bacterial adhesion under selection pressure on EABs has not been systematically studied. Here, the response of the composition, structure, and electrochemical performance of EABs to the selective adhesion pressure due to the selective coordination of Fe(III) and Co(II) with thiol and the different affinities for bacteria on hybrid electrodes (Fe1Co, Fe4Co, and Fe10Co) were comprehensively investigated. Compared with carbon cloth (CC), the appropriate selective adhesion pressure of Fe4Co activated the dead inner core of EABs and optimized their viability stratification structure. Both the total viability and the viability of the inner core layer in the Fe4Co EAB (0.67, 0.70 ± 0.01) were higher than those of the CC (0.46, 0.54 ± 0.01), Fe1Co (0.50, 0.48 ± 0.03), and Fe10Co (0.51, 0.51 ± 0.03). Moreover, a higher proportion of proteins was detected in the Fe4Co EAB, enhancing the redox activity of extracellular polymeric substances. Fe4Co enriched Geobacter and stimulated microbial metabolism. Electrochemical analysis revealed that the Fe4Co EAB was the most electroactive EAB, with a maximum power density of 2032.4 mW m-2, which was 1.7, 1.3, and 1.1 times that of the CC (1202.6 mW m-2), Fe1Co (1610.3 mW m-2), and Fe10Co (1824.4 mW m-2) EABs, respectively. Our findings confirmed that highly active EABs could be formed by imposing selection pressure on bacterial adhesion.
Asunto(s)
Materiales Biocompatibles/química , Biopelículas , Cobalto/química , Geobacter/química , Hierro/química , Adhesión Bacteriana , Fuentes de Energía Bioeléctrica , Electrodos , Geobacter/metabolismo , Ensayo de Materiales , PresiónRESUMEN
The effects of membrane permeability on extracellular electron transfer (EET) and performance of microbial fuel cell (MFC) need to be explored. In this work, cetyltrimethylammonium bromide (CTAB) was chosen to enhance the current generation and bidirectional transport of substrate and electron shuttles by tailoring the cell membrane permeability. Specifically, the peak currents of biofilms treated with CTAB especially at 200 µM were obviously higher than the control biofilm with no CTAB, and the riboflavin mediated electron transfer was promoted prominently. Biomass and viability analyses showed that an appropriate concentration of CTAB had almost no adverse effect on the cell viability of biofilm and could increase the biomass of biofilm. Measurements of the extracellular activity of alkaline phosphatase and UV-vis absorption confirmed the increased membrane permeability and the promoted efficiency of substrates transported into cells. This contribution paves the key step for facilitating EET process by adjusting membrane permeability through CTAB or other surfactants addition.
Asunto(s)
Fuentes de Energía Bioeléctrica , Electrones , Permeabilidad de la Membrana Celular , Cetrimonio , PermeabilidadRESUMEN
An extracellular electron transfer (EET) process between an electroactive biofilm and an electrode is a crucial step for the performance of microbial fuel cells (MFCs), which is highly related to the enrichment of exoelectrogens and the electrocatalytic activity of the electrode. Herein, an efficient N- and Fe-abundant carbon cloth (CC) electrode with the comodification of iron porphyrin (FePor) and polyquaternium-7 (PQ) was synthesized using a facile solvent evaporation and immersion method and developed as an anode (named FePor-PQ) in MFCs. The surface structural characterizations confirmed the successful introduction of N and Fe atoms, whereas FePor-PQ achieved the N content of 9.59 at %, which may offer various active sites for EET. The introduction of PQ contributed to improving the surface hydrophilicity, providing the composite electrode good biocompatibility for bacterial attachment and colonization as well as substrate diffusion. Based on the advantages, the MFC with the FePor-PQ anode produced a maximum power density of 2165.7 mW m-2, strikingly higher than those of CC (1124.0 mW m-2), PQ (1668.8 mW m-2), and FePor (1978.9 mW m-2). Furthermore, with the EET mediated by the binding of flavins and c-type cytochromes on the outer membrane was enhanced prominently, the typical exoelectrogen Geobacter was enriched up to 55.84% in the FePor-PQ anode biofilm. This work reveals a synergistic effect from heteroatom coating and surface properties tailoring to boost both the EET efficiency and exoelectrogen enrichment for enhancing MFC performance, which also provides valuable insights for designing electrodes in other bio-electrochemical systems.
Asunto(s)
Bacterias/química , Fuentes de Energía Bioeléctrica , Acrilamidas/síntesis química , Acrilamidas/química , Acrilamidas/metabolismo , Cloruro de Amonio/síntesis química , Cloruro de Amonio/química , Cloruro de Amonio/metabolismo , Bacterias/citología , Bacterias/metabolismo , Adhesión Bacteriana , Materiales Biocompatibles , Carbono/química , Electrodos , Transporte de Electrón , Electrones , Ensayo de Materiales , Metaloporfirinas/síntesis química , Metaloporfirinas/química , Metaloporfirinas/metabolismo , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
Robust lung inflammation is one of the prominent features in the pathogenesis of acute lung injury (ALI). Macrophage migration and recruitment are often seen at the early stage of lung inflammatory responses to noxious stimuli. Using an acid inhalation-induced lung injury model, we explored the mechanisms by which acid exposure initiates macrophage recruitment and migration during development of ALI. The lung epithelium comprises a large surface area and functions as a first-line defense against noxious insults. We found that acid exposure induced a remarkable microvesicle (MV) release from lung epithelium as detected in bronchoalveolar lavage fluid. Significantly elevated RNA, rather than protein, was found in these epithelium-derived MVs after acid and included several highly elevated microRNAs, including microRNA (miR)-17 and miR-221. Acid-induced epithelial MV release promoted macrophage migration in vitro and recruitment into the lung in vivo and required, in part, MV shuttling of miR-17 and/or miR-221. Mechanistically, acid-induced epithelial MV miR-17/221 promoted ß1 integrin recycling and presentation back onto the surface of macrophages, in part via a Rab11-mediated pathway. Integrin ß1 is known to play an essential role in regulating macrophage migration. Taken together, acid-induced ALI results in epithelial MV shuttling of miR-17/221 that in turn modulates macrophage ß1 integrin recycling, promoting macrophage recruitment and ultimately contributing to lung inflammation.
Asunto(s)
Lesión Pulmonar Aguda/inmunología , Micropartículas Derivadas de Células , Integrina beta1/metabolismo , Pulmón/citología , Macrófagos/fisiología , MicroARNs/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Animales , Líquido del Lavado Bronquioalveolar/inmunología , Movimiento Celular , Modelos Animales de Enfermedad , Células Epiteliales/inmunología , Células Epiteliales/fisiología , Ácido Clorhídrico/administración & dosificación , Inflamación/inmunología , Integrina beta1/inmunología , Pulmón/patología , Pulmón/fisiología , Macrófagos/inmunología , Ratones , MicroARNs/aislamiento & purificaciónRESUMEN
Bacterial pneumonia is a common and serious clinical entity. Alveolar epithelial cells and alveolar macrophages are the first line of defense in the innate immunity against bacterial pathogens. Epithelial cells are known to release chemokines/cytokines that recruit and activate phagocytic cells. However, the signals sent from alveolar macrophages back to the lung epithelial cells remain largely unexplored. We found that LPS, a well-recognized stimulator derived from gram-negative (G-) bacteria, rapidly and robustly induces the secretion of macrophage-derived extracellular vesicles (EVs). The main type of EVs found in the early stages after LPS stimulation are apoptotic bodies (ABs) and not microvesicles (MVs) or exosomes (Exos). Furthermore, LPS markedly up-regulate the levels of a repertoire of microRNAs (miRNAs) in the macrophage-derived ABs, including miR-221 and miR-222. Functionally, the LPS-induced, macrophage-derived ABs promote the proliferation of malignant and/or normal lung epithelial cells. We next directly transfected miR-221 and/or miR-222 inhibitors into the LPS-induced ABs. Deletion of miR-221/222 in ABs significantly reduces the AB-mediated proliferation of lung epithelial cells. Mechanistically, AB-shuttling miR-221/222 promote cell growth by modulating cyclin-dependent kinase inhibitor 1B (CDKN1B) pathways. Collectively, LPS-induced, macrophage-derived ABs promote the proliferation of their recipient epithelial cells, partially via AB-shuttling miRNAs.